The risk of recurrence is greatest immediately after stroke or Transient Ischaemic Attack (TIA). Existing prevention strategies (antithrombotic, lipid/blood pressure lowering, endarterectomy) reduce, not abolish, further events. Dual antiplatelet therapy - aspirin & clopidogrel (AC) for IHD, aspirin & dipyridamole (AD) for stroke, is superior to aspirin monotherapy. The investigators hypothesise that triple antiplatelet therapy (ACD) will be superior to AD in patients at high-risk of recurrence, providing bleeding does not become excessive.

Design: TARDIS is a multicentre, parallel-group, prospective, randomised, open-label, blinded-endpoint, controlled trial. In the start-up phase, the investigators will assess over 3 years the safety, tolerability and feasibility of intensive therapy (ACD) versus guideline therapy (AD) given for 1 month in 750 patients with acute stroke/TIA. The main phase will then assess the safety and efficacy of ACD in up to 3500 patients. The primary outcome is ordinal stroke (fatal/severe non-fatal/mild/TIA/none) at 90 days. Secondary outcomes include death, MI, vascular events, function, bleeding, serious adverse events; sub-studies will assess cerebral emboli and platelet function.

Participants in the intensive antiplatelet group will receive Aspirin+Dipyridamole+Clopidogrel triple therapy for 28-30 days (to cover the period of maximum risk of recurrence) along with standard 'best care' (including lifestyle advice, BP and lipid lowering). Clop will be given as a loading dose of 300 mg,12 then 75 mg daily, Asp as a loading dose of 300 mg,22 then 75 mg daily, and Dip modified release 200 mg twice daily 9 for 28-30 days.

Drug: Aspirin, Dipyradimole, Clopidogrel

Participants in the intensive antiplatelet group will receive Asp+Dip+Clop triple therapy for 28-30 days (to cover the period of maximum risk of recurrence) along with standard 'best care' (including lifestyle advice, BP and lipid lowering). Clop will be given as a loading dose of 300 mg,12 then 75 mg daily, Asp as a loading dose of 300 mg,22 then 75 mg daily, and Dip modified release 200 mg twice daily 9 for 28-30 days.

Other Names:

Aspirin

Dipyradimole

Clopidogrel

No Intervention: Guideline antiplatelet therapy

Two antiplatelet drugs, as per standard treatment

Detailed Description:

2.1 Purpose To perform a randomised trial assessing the efficacy, safety and tolerability of intensive antiplatelet therapy (Asp+Dip+Clop) versus guideline antiplatelet therapy (Asp+Dip or Clop) in patients with recent ischaemic stroke or TIA and who are at high risk of recurrence.

Informed consent from participant. If the participant is unable to give meaningful consent e.g. due to dysphasia, confusion, or reduced conscious level, proxy consent may be obtained from a relative, carer or legal representative.

Stroke secondary to a procedure (e.g. carotid or coronary intervention)

Coma (GCS < 8)

Non-stroke life expectancy < 6 months

Dementia

Participation in another drug or devices trial concurrently or within 30 days. (participants may take part in observational studies or non-drug or devices trials)

Geographical or other factors that may interfere with follow-up e.g. no fixed address or telephone contact number, not registered with a GP, or overseas visitor.

Females of childbearing potential, pregnancy or breastfeeding

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01661322